Evidence map›Paper›PMID 29253225›Full record

ArticleNucleic acids research2018

Single-molecule DNA unzipping reveals asymmetric modulation of a transcription factor by its binding site sequence and context.

Sergei Rudnizky, Hadeel Khamis, Omri Malik, Allison H Squires, Amit Meller, Philippa Melamed, Ariel Kaplan

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.1field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 28 citations in OpenAlex.

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  15. How affinity of the ELT-2 GATA factor binding toDevelopment (Cambridge, England) · 2020
    Article
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  17. The base pair-scale diffusion of nucleosomes modulates binding of transcription factors.Proceedings of the National Academy of Sciences of the United States of America · 2019
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Sergei RudnizkyFaculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Hadeel KhamisFaculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Omri MalikFaculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Allison H SquiresDepartment of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
Amit MellerRussell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Philippa MelamedFaculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Ariel KaplanFaculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Technion – Israel Institute of Technology · ILBoston University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Most functional transcription factor (TF) binding sites deviate from their 'consensus' recognition motif, although their sites and flanking sequences are often conserved across species. Here, we used single-molecule DNA unzipping with optical tweezers to study how Egr-1, a TF harboring three zinc fingers (ZF1, ZF2 and ZF3), is modulated by the sequence and context of its functional sites in the Lhb gene promoter. We find that both the core 9 bp bound to Egr-1 in each of the sites, and the base pairs flanking them, modulate the affinity and structure of the protein-DNA complex. The effect of the flanking sequences is asymmetric, with a stronger effect for the sequence flanking ZF3. Characterization of the dissociation time of Egr-1 revealed that a local, mechanical perturbation of the interactions of ZF3 destabilizes the complex more effectively than a perturbation of the ZF1 interactions. Our results reveal a novel role for ZF3 in the interaction of Egr-1 with other proteins and the DNA, providing insight on the regulation of Lhb and other genes by Egr-1. Moreover, our findings reveal the potential of small changes in DNA sequence to alter transcriptional regulation, and may shed light on the organization of regulatory elements at promoters.

Indexed as

Transcription, GeneticBase SequenceBinding SitesDNAEarly Growth Response Protein 1Gene Expression RegulationHumansKineticsNucleic Acid ConformationOptical TweezersPromoter Regions, GeneticProtein BindingProtein Interaction Domains and MotifsSingle Molecule ImagingSubstrate SpecificityThermodynamicsDNAEarly Growth Response Protein 1EGR1 protein, human

Identifiers

PMID29253225
PMCPMC5815098
OpenAlexW2791570688

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.